Anti-CTLA-4 Antibodies Induce a Sustained, NK Cell- and T Cell-Dependent Vaccinal Effect for Tumor Prevention and Therapy

preprint OA: closed CC-BY-4.0
📄 Open PDF Full text JSON View at publisher

Abstract

Abstract Anti-CTLA-4 antibodies have been widely utilized in cancer therapy owing to their capacity to activate tumor immunity by reversing intratumoral immune suppression. However, whether these antibodies can exert an anti-tumor vaccinal effect—with considerable clinical implications for preventing tumor recurrence—remains largely unexplored. In the present study, anti-CTLA-4 antibody treatment induced complete regression of established Hepa1-6 tumors in a subset of mice. More notably, cured mice developed a robust anti-tumor vaccinal effect persisting over 50 weeks. Critically, anti-CTLA-4 pretreatment inhibited tumor growth, drove regression and conferred potent vaccinal effect upon rechallenge with the same tumor cells. Furthermore, tumor-specific immune mice were protected against distant metastasis. Mechanistically, complete regression correlated with increased effector memory T cell proportions. Depletion experiments confirmed that T and NK cell depletion fully abrogated the antibody-induced vaccinal effect. Most intriguingly, adoptive transfer of PBMCs from immune mice into naive recipients via tail vein injection conferred Hepa1-6-specific immunity. Collectively, our findings establish the vaccinal potential of anti-CTLA-4 antibody and provide a promising strategy to prevent tumor recurrence.
Full text 14,507 characters · extracted from preprint-html · click to expand
Anti-CTLA-4 Antibodies Induce a Sustained, NK Cell- and T Cell-Dependent Vaccinal Effect for Tumor Prevention and Therapy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Brief Communication Anti-CTLA-4 Antibodies Induce a Sustained, NK Cell- and T Cell-Dependent Vaccinal Effect for Tumor Prevention and Therapy Gong Peng, Zhao li Meng, Fang Xie This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8432100/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Anti-CTLA-4 antibodies have been widely utilized in cancer therapy owing to their capacity to activate tumor immunity by reversing intratumoral immune suppression. However, whether these antibodies can exert an anti-tumor vaccinal effect—with considerable clinical implications for preventing tumor recurrence—remains largely unexplored. In the present study, anti-CTLA-4 antibody treatment induced complete regression of established Hepa1-6 tumors in a subset of mice. More notably, cured mice developed a robust anti-tumor vaccinal effect persisting over 50 weeks. Critically, anti-CTLA-4 pretreatment inhibited tumor growth, drove regression and conferred potent vaccinal effect upon rechallenge with the same tumor cells. Furthermore, tumor-specific immune mice were protected against distant metastasis. Mechanistically, complete regression correlated with increased effector memory T cell proportions. Depletion experiments confirmed that T and NK cell depletion fully abrogated the antibody-induced vaccinal effect. Most intriguingly, adoptive transfer of PBMCs from immune mice into naive recipients via tail vein injection conferred Hepa1-6-specific immunity. Collectively, our findings establish the vaccinal potential of anti-CTLA-4 antibody and provide a promising strategy to prevent tumor recurrence. Biological sciences/Cancer/Cancer therapy/Cancer immunotherapy Biological sciences/Cancer/Cancer prevention Figures Figure 1 Figure 2 Figure 3 Figure 4 Full Text Additional Declarations There is NO conflict of interest to disclose. Supplementary Files supplementalmaterials.pdf supplemental figures Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8432100","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Brief Communication","associatedPublications":[],"authors":[{"id":570952109,"identity":"0df90c52-dcc5-45f5-ae33-d096c7325728","order_by":0,"name":"Gong Peng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAt0lEQVRIiWNgGAWjYBACPghlwwxm8BCjhQ1CpTGzkarlMAMJWthPJz74uOM8O5tEAuODt20M8uYEtfDkbjaceeY2M1ALs+HcNgbDnQ0EHZa7TZq3DayFDchgSDA4QEgL/1uQlnMgLey/idMiAbblANgWZiK1vAX6pS2ZmY3nYbPknHMShhsIaeHnz9344GObXTI/e/LBD2/KbOQJ2gIDyQwMjA1AWoJI9UBgR7zSUTAKRsEoGHEAAL+5M8HugS8SAAAAAElFTkSuQmCC","orcid":"","institution":"Laboratory of Tumor Immunology, The First Hospital of Jilin University","correspondingAuthor":true,"prefix":"","firstName":"Gong","middleName":"","lastName":"Peng","suffix":""},{"id":570952110,"identity":"3f56cde7-a95d-4ec9-bfaf-9db65dde8fd0","order_by":1,"name":"Zhao li Meng","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Zhao","middleName":"li","lastName":"Meng","suffix":""},{"id":570952111,"identity":"fac61c2d-0a28-48c1-9845-a17f70844ced","order_by":2,"name":"Fang Xie","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Fang","middleName":"","lastName":"Xie","suffix":""}],"badges":[],"createdAt":"2025-12-23 09:30:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8432100/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8432100/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":100359044,"identity":"7d1052ec-3f1a-4d3d-80cf-c6b26fec4093","added_by":"auto","created_at":"2026-01-16 07:21:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":792743,"visible":true,"origin":"","legend":"","description":"","filename":"Figures.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8432100/v1/46b23f128db2654c0e45b7e2.pdf"},{"id":99889750,"identity":"e5ae34ed-c35b-46b0-a5f4-1ee065ef7839","added_by":"auto","created_at":"2026-01-09 13:27:44","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":353561,"visible":true,"origin":"","legend":"","description":"","filename":"maintext.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8432100/v1/aa9bae3d94a91714bbb54de9.pdf"},{"id":100358707,"identity":"a8971988-1165-4239-9f4e-5f3c3d2818b5","added_by":"auto","created_at":"2026-01-16 07:21:16","extension":"json","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":4898,"visible":true,"origin":"","legend":"","description":"","filename":"ONC202504066.json","url":"https://assets-eu.researchsquare.com/files/rs-8432100/v1/2bde67cd7e8497e0954d0d9c.json"},{"id":99889751,"identity":"af3b37d1-f829-4117-9cf1-c243ed3198d7","added_by":"auto","created_at":"2026-01-09 13:27:44","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":620374,"visible":true,"origin":"","legend":"","description":"","filename":"supplementalmaterials.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8432100/v1/cf48d10a8733a521e12a76b7.pdf"},{"id":99889743,"identity":"b53d3221-5d42-4123-9b99-cbbc37e49146","added_by":"auto","created_at":"2026-01-09 13:27:44","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":254141,"visible":true,"origin":"","legend":"\u003cp\u003eFigure legend not provided with this version\u003c/p\u003e","description":"","filename":"Figures1.png","url":"https://assets-eu.researchsquare.com/files/rs-8432100/v1/a1f2587c160f4ac6ed5d07b6.png"},{"id":99889744,"identity":"c6301ca3-0aae-468e-b0b9-f22da28b482d","added_by":"auto","created_at":"2026-01-09 13:27:44","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":304153,"visible":true,"origin":"","legend":"\u003cp\u003eFigure legend not provided with this version\u003c/p\u003e","description":"","filename":"Figures2.png","url":"https://assets-eu.researchsquare.com/files/rs-8432100/v1/c9a673bb177875f7a87108bb.png"},{"id":99889745,"identity":"9946f1bb-88c7-4779-ac18-60a210fe21a1","added_by":"auto","created_at":"2026-01-09 13:27:44","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":252702,"visible":true,"origin":"","legend":"\u003cp\u003eFigure legend not provided with this version\u003c/p\u003e","description":"","filename":"Figures3.png","url":"https://assets-eu.researchsquare.com/files/rs-8432100/v1/f9d414b53c25df9ec8a80f06.png"},{"id":100358305,"identity":"472551c2-b09d-40d6-bb22-7d9108fd8095","added_by":"auto","created_at":"2026-01-16 07:20:53","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":932521,"visible":true,"origin":"","legend":"\u003cp\u003eFigure legend not provided with this version\u003c/p\u003e","description":"","filename":"Figures4.png","url":"https://assets-eu.researchsquare.com/files/rs-8432100/v1/373aea5e6676addfa455b235.png"},{"id":100377371,"identity":"70dedddd-f593-4230-b556-5181a0c5a9b8","added_by":"auto","created_at":"2026-01-16 08:47:47","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1089676,"visible":true,"origin":"","legend":"Article File","description":"","filename":"maintext.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8432100/v1_covered_aa11c4ed-b9a6-4130-903c-be5ffec546f4.pdf"},{"id":99889747,"identity":"8aa391d7-0d91-4592-9b3a-e02d16b5f287","added_by":"auto","created_at":"2026-01-09 13:27:44","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":620374,"visible":true,"origin":"","legend":"supplemental figures","description":"","filename":"supplementalmaterials.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8432100/v1/8b3e25cd4495c04d7983de26.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Anti-CTLA-4 Antibodies Induce a Sustained, NK Cell- and T Cell-Dependent Vaccinal Effect for Tumor Prevention and Therapy","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8432100/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8432100/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Anti-CTLA-4 antibodies have been widely utilized in cancer therapy owing to their capacity to activate tumor immunity by reversing intratumoral immune suppression. However, whether these antibodies can exert an anti-tumor vaccinal effect—with considerable clinical implications for preventing tumor recurrence—remains largely unexplored. In the present study, anti-CTLA-4 antibody treatment induced complete regression of established Hepa1-6 tumors in a subset of mice. More notably, cured mice developed a robust anti-tumor vaccinal effect persisting over 50 weeks. Critically, anti-CTLA-4 pretreatment inhibited tumor growth, drove regression and conferred potent vaccinal effect upon rechallenge with the same tumor cells. Furthermore, tumor-specific immune mice were protected against distant metastasis. Mechanistically, complete regression correlated with increased effector memory T cell proportions. Depletion experiments confirmed that T and NK cell depletion fully abrogated the antibody-induced vaccinal effect. Most intriguingly, adoptive transfer of PBMCs from immune mice into naive recipients via tail vein injection conferred Hepa1-6-specific immunity. Collectively, our findings establish the vaccinal potential of anti-CTLA-4 antibody and provide a promising strategy to prevent tumor recurrence.","manuscriptTitle":"Anti-CTLA-4 Antibodies Induce a Sustained, NK Cell- and T Cell-Dependent Vaccinal Effect for Tumor Prevention and Therapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-09 13:27:39","doi":"10.21203/rs.3.rs-8432100/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"907d7d95-fa44-4ad8-b74e-0ed23692f940","owner":[],"postedDate":"January 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":60757392,"name":"Biological sciences/Cancer/Cancer therapy/Cancer immunotherapy"},{"id":60757393,"name":"Biological sciences/Cancer/Cancer prevention"}],"tags":[],"updatedAt":"2026-01-09T13:27:39+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-09 13:27:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8432100","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8432100","identity":"rs-8432100","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: preprint-html

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2026) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

europepmc
last seen: 2026-05-20T01:45:00.602351+00:00
unpaywall
last seen: 2026-05-20T11:00:21.680559+00:00
License: CC-BY-4.0